It is known that a hypothalamic hormone or a pituitary hormone is concerned in the secretion controlling mechanism of peripheral hormones. In general, secretion of anterior pituitary hormones is controlled by a secretion accelerating hormone or a secretion inhibiting hormone secreted from its upper central hypothalamus or by a peripheral hormone secreted from a target organ of respective hormone.
Gonadotropin releasing hormone (to be referred to as GnRH hereinafter, and GnRH is also called luteinizing hormone releasing hormone; LHRH) is known as a hormone which controls secretion of sex hormones at the highest position, and controls secretion of anterior pituitary hormones luteinizing hormone (to be referred to as LH hereinafter) and follicle-stimulating hormone (to be referred to as FSH hereinafter) and sex hormones in sex glands, via a receptor which is present in the anterior pituitary (to be referred to as GnRH receptor hereinafter) (Hormone To Rinsho (Hormone and Clinics), a special number for spring, 46, 46-57 (1998)). Since antagonists specific and selective for this GnRH receptor regulate the action of GnRH and control secretion of subordinate LH and FSH and sex hormones, they are expected as preventive or therapeutic agents for sex hormone dependent diseases (aforementioned Hormone and Clinics, a special number for spring (1998)).
To date, peptide compounds cetrorelix (Non-patent Reference 1) and abarelix (Non-patent Reference 2) have been put on the market as GnRH receptor antagonists.
On the other hand, as non-peptide compounds having GnRH receptor antagonism, a thienopyrimidine derivative TAK-013 (Non-patent Reference 3) and a uracil derivative NBI-42902 (Non-patent Reference 4) are now under clinical tests.
In addition, Patent Reference 1 discloses that a propane-1,3-dione derivative has the GnRH receptor antagonism.
(In the formula, A and B may be the same or different from each other and each represents an aryl which may be substituted or a heteroaryl which may be substituted.)
However, there is no illustrative disclosure on a compound which has a 1-hydroxyalkyl group as a substituent group in the ring A or ring B.
[Non-patent Reference 1] Proc. Natl. Acad. Sci., USA, 85, 1637-1641, 1988
[Non-patent Reference 2] J. Urol., 167, 1670-1674, 2002
[Non-patent Reference 3] J. Clin. Endocrinol. Metab., 88, 1697-1704, 2003
[Non-patent Reference 4] J. Med. Chem., 2005, 48, 1169-1178
[Patent Reference 1] International Publication WO 02/02533